Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

2007 ◽  
Vol 87 (5) ◽  
pp. 361-367 ◽  
Author(s):  
Jerzy Hołowiecki ◽  
Sebastian Grosicki ◽  
Sławomira Kyrcz-Krzemien ◽  
Aleksander B. Skotnicki ◽  
Beata Piatkowska-Jakubas ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pilot Study ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Early Outcome ◽  
Refractory Acute Myeloid Leukemia ◽  
Adult Leukemia ◽  
Leukemia Group ◽  
Acute Myeloid

Prospective, Randomized, Multicenter Phase III, Polish Adult Leukemia Group (PALG) Study Comparing DAF (DNR+AraC+Fludarabine), DAC (DNR+AraC+Cladribine), and Standard DA Regimen in Induction of Untreated Acute Myeloid Leukemia Patients - First Report.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4616-4616
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Grosicki ◽  
Slawomira Kyrcz-Krzemien ◽  
Janusz Kloczko ◽  
Kazimierz Sulek ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Study Groups ◽  
Primary Objective ◽  
Phase Iii ◽  
Who Grade ◽  
Adult Leukemia ◽  
Leukemia Group ◽  
Acute Myeloid

Abstract The goal of this study is to compare the efficacy and safety of an original DAF regimen: daunorubicine (DNR) 60 mg/m2/d iv, days 1–3; cytarabine (AraC) 200 mg/m2/d ci, d 1–7, and fludarabine 25 mg/m2 2h inf. iv d 1–5 versus previously studied DAC regimen* (DNR, AraC, Cladribine), and versus standard DA in de novo acute myeloid leukemia (AML) patients below 60. Primary objective is complete remission (CR) rate after single course of induction and overall survival, secondary objectives - overall CR rate, toxicity, leukemia-free survival rate, assessment of lymphocyte subpopulations levels and survival in patients submitted to bone marrow allotransplantation (alloBMT) immediately after CR assessment. Patients achieving CR and did not submit to alloBMT received two courses of subsequent intensive consolidation: 1) HAM (HD AraC, mitoxantrone) 2) HD AraC. In case of partial remission (PR) after the first induction course the same regimen was repeated, Patients with no remission (NR) or PR/NR after 2 induction courses were withdrawn with the study. We are planning to enrol to the study 600 patients in 3 years. Between 09.2004 and 07.2005, 147 adult AML patients, aged 48 (19–60)y, sex: male 57, female 90, treated in 16 co-operating Polish Adult leukemia Group (PALG) centres were randomised to either DAF (n=44), DAC (n=49) or DA (n=54) arm. PML/RAR alfa positive - FAB M3 cases were excluded. Both study groups were well balanced in respect of age, sex, FAB subtype, and WBC. The final CR rate and CR rate after the first induction course equalled: for DAF 65% and 60%, for DAC 70% and 60%, and for DA 55% and 47%, respectively (p=NS). The median times to ANC recovery > 0.5 G/L, and PLT >50 G/L in each arms were similar (22–26 d.) (p=NS). All patients developed WHO grade IV thrombocytopenia and agranulocytosis. The frequency and severity of infections, mucositis, vomiting, diarrhea, alopecia, polyneuropathy as well as of cardiac, liver or kidney failure were comparable in each treatment arms. Early death was noted in 6% (n=2) in DAF, in 9% (n=3) in DAC, and in 13% (n=5) in DA group, because of bacterial sepsis in every cases. In conclusion, this original study proves that the addition of fludarabine to the standard DNR+AraC regimen (DAF) comparing to DAC and DA regimen is a potent antileukemic treatment without increased toxicity.

Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group.

1985 ◽  
Vol 3 (12) ◽  
pp. 1583-1589 ◽  
Author(s):  
T Büchner ◽  
D Urbanitz ◽  
W Hiddemann ◽  
H Rühl ◽  
W D Ludwig ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pilot Study ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Randomized Study ◽  
Remission Induction ◽  
Multicenter Studies ◽  
Remission Duration ◽  
Table Analysis ◽  
Acute Myeloid

In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.

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